There are a number of examples in the literature of the preparation of allylic alcohols from epoxides and methyl sulfoxides. For example, Takano, S.; Tomita, S.; Iwabuchi, Y.; Ogasawara, K. Synthesis 610-611 (1988), report the use of sodium dismylate, obtained from dimethylsulfoxide and sodium hydride, to open the epoxide 1 to give the .gamma.-hydroxysulfoxide 2. Heating 2 in refluxing 1,2-dichlorobenzene gives the allylic alcohol 3. (See, Scheme I). ##STR1##
Guittet, E.; Julia, Sylvestre, J. Synth. Comm. 9:317-323 (1979), disclose the reaction of the lithium anion of the sulfoxide 4 with epoxide 5. The product (6) is then heated in refluxing toluene to give 3,7-dimethylocta-1,5(E),7-trien-3-ol (7). (See, Scheme II.) ##STR2##
Other references disclose the preparation of .gamma.-hydroxysulfoxides, but do not mention the thermolysis of these compounds to give the corresponding olefin. For example, German patent 2,541,659, Apr. 8, 1976, discloses the opening of epoxide 10 with methyl tert-butyl sulfoxide anion to give sulfoxide 11 which was cyclized to a sulfinate ester 12 (Scheme III). ##STR3##
Sharma, N. K.; de Reinach-Hirtzbach, F.; Durst, T., Can. J. Chem. 54:3012 (1976) disclose the reaction of methyl tert-butyl sulfoxide anion with propylene oxide and styrene oxide.
Okamura, H. et al. Chem. Lett. 517-520 (1978), disclose the reaction of the lithium anion of vinyl aryl sulfoxides with propylene oxide and styrene oxide.
There are a very large number of literature references describing the thermal elimination of sulfoxides to form alkenes. See, for example, Trost, B. M.; Salzmann, T. N.; Hiroi, K. J. Am. Chem. Soc. 98:4887 (1976) and the references cited therein.
When attempting to utilize the teachings of the prior art mentioned above, certain difficulties were encountered. For example, (3-R)-20,20-ethylenedioxy-5.alpha.-pregnane-spiro-2'-oxirane was treated with sodium dismylate to give 20,20-ethylenedioxy-3.beta.-hydroxy-3.beta.-[2-(methylsulfinyl)ethyl]-5.al pha.-pregnane. When this compound was refluxed with calcium carbonate in p-isopropyltoluene (see Takano et al., supra), extensive dehydration of the tertiary alcohol occurred. Adding 2,4,6-collidine to the reaction mixture did not prevent the dehydration.
An object of the present invention is to provide a novel and mild method to generate steroidal allylic tertiary alcohols without dehydration.